An increasing number of primary arylamines have been shown to produce cancer when ingested by animals or man. Carcinogenesis is apparently associated with the metabolic conversion of the amine to an arylhydroxylamine (AH) which is further transformed to an electrophilic species capable of arylating nucleic acid residues. This activation of AH's is at least in part under metabolic control. In preliminary studies of the metabolism of 2-aminoindan and 2-hydroxylamineindan in rat liver homogenates, we have isolated a number of products, including nitroso, nitro, axo- and azoxy compunds, that have potential carcinogenic activity of may be produced from these precursors with concomitant generation of reactive intermediates with potentially toxic properites. Furthermore, we have established that these products are formed efficiently in the absence of biological material. Therefore, because of the complex chemical transformations that AN's undergo in aqueous solution (in the absence of enzymes), their chemical behavior must be characterized, to provide the foundation upon which a rational investigation of their metabolism can be based. The objective of this proposal is to study the chemistry of AH's in aqueous buffer solution with emphasis on product identification and kinetic and thermodynamic (product yield and distribution) aspects. A composite of the chemical behavior of the AH will be constructed after studying (a) AH oxidation to yield nitroso and nitro compounds, (b) AH condensation with nitroso compounds, (c) AH rearrangement to aminophenols, and (d) amine condensation with nitroso compounds both individually and as total degradation.